title: Pharmacokinetics, clinical indications, and resistance mechanisms in molecular targeted therapies in cancer.
abstract: The strategy for discovery and development of new cancer drugs has shifted the field from cytotoxic agents to therapies that selectively target oncogenic drivers. In the last decade, a number of targeted cancer therapies have been discovered and proven effective in a variety of hematological and solid malignancies. In this article, we review clinical pharmacokinetic characteristics of the U.S. Food and Drug Administration-approved targeted therapies and provide an overview of key clinical trials that led to approval of these drugs. The major limiting factor of targeted treatment is the development of resistance. We describe general principles of resistance and specific, clinically confirmed mechanisms of resistance to several therapies in different malignancies.
authors.affiliation: 10 North Grove Street, LRH 214, Boston, MA, 02114. bchabner@partners.org.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Izar
authors.forename: Julia
authors.initials: J
authors.lastname: Rotow
authors.forename: Justin
authors.initials: J
authors.lastname: Gainor
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Clark
authors.forename: Bruce
authors.initials: B
authors.lastname: Chabner
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents